Plasma cytokine concentrations and quality of life in patients with non-small cell lung cancer in a phase II trial of first-line treatment with carboplatin-paclitaxel and/or vandetanib.
Hanrahan EO., Kim F., Lin HY., Tran HT., Ryan AJ., Krebs AD., Lee JJ., Johnson BE., Heymach JV., Kim ES.
9596 Background: A randomized phase II trial (JCO 26:5407-15, 2008) compared carboplatin-paclitaxel (CP) with vandetanib (VEGFR-EGFR inhibitor) monotherapy (V) and V plus CP (VCP) 1st-line for advanced NSCLC (N=181). PFS was superior for VCP vs CP (HR 0.76). We performed analyses of quality of life (QOL) and its correlations with plasma concentrations of cytokines and angiogenic factors (CAF) among the participants in this trial. METHODS: QOL was serially measured by Functional Assessment of Cancer Therapy-Lung (FACT-L) and Trial Outcome Index (TOI) scores. Concentrations of 35 plasma CAFs were measured at baseline and multiple timepoints during treatment with multiplexed bead suspension arrays and ELISAs. We performed exploratory analyses for the following associations: (1) QOL with plasma CAF levels at baseline; (2) changes in QOL with changes in plasma CAF levels. Spearman correlation coefficient, log-rank test and mixed linear models were applied in the analyses. P-value < 0.05 was considered significant. RESULTS: Baseline QOL and plasma samples were both available for 120 patients. Lower baseline FACT-L scores (inferior QOL) were associated with higher pre-treatment plasma levels of INF-γ, IL-1RA, IL-6, IL-12, IL-15, TNF-α, RANTES, MIG, MIP-1β, MMP-9, bFGF, VEGF and sVEGFR-2 (all P<0.05). Lower baseline TOI scores (inferior QOL) were also associated with higher pre-treatment plasma levels of multiple CAFs, including GCSF, HGF, INF-α, INF-γ, IL-2, IL-6, IL-8, IL-12, IL-15, TNF-α, bFGF, sVEGFR-2 and VEGF (all P<0.05). Among all patients, decreasing TOI scores post cycle 2 (HR=2.57 [1.28,5.17], P=0.008) and cycle 4 (HR=2.58 [1.01,6.56], P=0.049) were associated with increased progression risk. Trends for FACT-L were similar, but did not reach statistical significance. Rises in GCSF, HGF, IL-2, IL-8, IL-15, MCP-1, MIP-1β, and VEGF from baseline to post cycle 2 were associated with decreased FACT-L and/or TOI scores (all P<0.05). CONCLUSIONS: High plasma concentrations of multiple CAFs pre-treatment in patients with NSCLC correlated with inferior QOL, and rises in these factors during treatment were associated with worsening QOL. This work was funded in part by grant from ACS (FK). [Table: see text].